Disorders of mineral metabolism have been evaluated with methods extending from epidemiology to cellular and molecular biology. Two extending from epidemiology to cellular and molecular biology. Two forms of familial hyperparathyroidism have been characterized in detail. Familial hypocalciuric hypercalcemia is an autosomal dominant trait associated with abnormal interactions with calcium in parathyroid and kidney. The affected gene in most kindreds encodes a G-protein linked calcium sensor, and missense mutations have been identified in many kindreds. Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant trait causing hyperfunction of parathyroids, pancreatic islet and anterior pituitary. It is associated with gradual but abnormal proliferation of the tissues affected. Plasma from affected persons shows high mitogenic activity upon cultured bovine parathyroid cells. This mitogenic activity in plasma may contribute to primary hyperparathyroidism in FMEN1. Analysis of blood and parathyroid tumor DNA has revealed that FMEN1 parathyroids often show clonal loss of alleles in the region of the FMEN1 gene on chromosome 11. Thus the FMEN1 gene probably functions as a tumor suppressor gene, analogous to the retinoblastoma gene. Analysis of sporadic parathyroid adenomas revealed that 25% showed allelic loss in a similar region. Thus the clonal inactivation of the FMEN1 gene may also be a contributing factor in many sporadic parathyroid adenomas. Tumors with allelic loss along chromosome 11 are being used to help delineate the minimal region of allelic loss which must harbor the men1 candidate gene.